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CURSO DE POSTGRADO 41 CONGRESO ANUAL AEEH ¿Qué utilidad tienen los métodos elastográficos en el paciente con enfermedad hepática avanzada? EHCAc/cACLD Joan Genescà Hospital Universitari Vall d’Hebron, VHIR, UAB, CIBERehd, Barcelona THE FRENCH CHEESESCAN CONECTION IT'S UN BRIE LIEVA BLE;; [euro] 95,000 cheese scanner can spot liver disease as well. Les quatre fondateurs d’Echosens® dans les locaux de l’Ecole Supérieure de Physique et de Chimie Industrielles (ESPCI) : de gauche à droite : Jean-Michel Hasquenoph, Bertrand Fourquet, Laurent Sandrin, Sylvain Yon PhD 1998-2000 Echosens 2001 Artículo científico Modelo comercial 2003 Esquema •Situación pre-‐elastografía •Impacto elastografía cACLD •Cambio epidemiológico • Prevalencia EHC poblacional • Prevalencia cACLD en EHC •Concepto cACLD: Compensated advanced chronic liver disease (fibrosis grave + cirrosis compensada) •Pronóstico/seguimiento/manejo •Varices/CSPH y elastografía Situación pre-elastografía Sospecha/diagnóstico cACLD/cirrosis • Datos clínicos (analíticos, imagen) • PBH • Al descompensarse • No se diagnosticaba Elastografía-cACLD Situación pre-elastografía • Joven • ALT 45 • VHB • Eco normal • Control Elastografía-cACLD Situación pre-elastografía • Adulto DBT • ALT 35 • GGT 60 • Eco esteatosis • Control, peso Situación pre-elastografía-HCC cribado 905 (75%) known cirrhosis 1500 VA HCC patients 1201 (80%) cirrhosis HCV 72% 296 (25%) unknown cirrhosis Walker, et al. Aliment Pharmacol Ther 2016 81% HCC BCLC B-‐D 61% HCC surveillance 97% HCC BCLC B-‐D 18% HCC surveillance Elastografía-cACLD Impacto elastografía-Epidemiología TRANSIENT ELASTOGRAPHY LIVER BIOPSY CLINICAL DIAGNOSIS F0/1 F2 F3 ACLD-LC Elastografía-cACLD Impacto elastografía-Población general Estudio N F/kPa % Roulot, 2011 1190 ≥8 >13 7,5 0,76 Baba, 2011 423 ≥F2 14,3 Wong, 2012 922 ≥9,6 1,62 Fung, 2014 2493 ≥8,7 ≥10,3 1,2 0,17 You, 2015 159 ≥F2 ≥8 7 1,9 Koelher, 2015 3041 ≥8 ≥13 5,6 0,6 Mayoría NAFLD Elastografía-cACLD Impacto elastografía-Población de riesgo PRECISED • 124 pacientes (105 diabéticos /19 controles) Elastografía (kPa) Diabéticos n = 105 Controles n = 19 P 5,6 (2,7) 4 (2,5) 0,002 Elasticidad ≥10 kPa • Pacientes con LSM ≥10 kPa: – 0 controles (0%) Diabéticos n = 13 (12,4%) Mediana (kPa) 16,5 Mínimo (kPa) 10,3 Máximo (kPa) 75 IQR (kPa) 6,9 Datos internos, Servicio Hepatología-HUVH, feb. 2016 Impacto elastografía-EHC A. CHRONIC LIVER DISEASE WITH NO SIGNS OF LIVER CIRRHOSIS *Patients with LSM≥13-13.6 kPa *8% *14% *10% n=173 Augustin, et al n=702 Chen, et al n=2876 Kim, et al B. PATIENTS WITH LSM≥13-13.6 kPa *Patients with occult ACLD (no signs of liver cirrhosis) *24% *37% n=54 Augustin, et al n=270 Chen, et al *15% n=221 ANTICIPATE Elastografía-cACLD Impacto elastografía-EHC Chen T, et al. Liver Int 2015 Elastografía-cACLD Impacto elastografía-cACLD Efectos de tests no invasivos (TE) en EHC -Situación clínica nueva en EHC -Más pacientes detectados en fases tempranas de cirrosis/cACLD -No todos son cirróticos -Recomendaciones de cribaje Impacto-elastografía-cACLD ¿PORQUÉ cACLD? cACLD: compensated advanced chronic liver disease -Enmarcar una situación clínica -Seleccionar pacientes para estudios clínicos y terapeúticos -Proporcionar recomendaciones de cribaje Impacto elastografía-cACLD ¿PORQUÉ cACLD Y NO CIRROSIS? 1) C irrosis es un diagnóstico histológico 2) No siempre hay cirrosis en los pacientes clasificados como F4 por tests no invasivos 3) No hay consenso sobre una definición clínica de cirrosis 4) Pacientes en estadios pre-‐cirróticos pueden tener hipertensión portal 5) C ribaje de HCC puede estar indicada en estadios pre-‐cirróticos 6) Los tests no invasivos han cambiado el escenario clínico de la EHC cACLD-concepto-Baveno VI-2015 • TE permite identificación en fases tempranas de pacientes con EHC en riesgo de desarrollar CSPH • Término refleja que el espectro de fibrosis grave y cirrosis es un continuo clinicamente indistinguible • cACLD y cirrosis compensada: términos aceptados • Pacientes con sospecha de cACLD: remitir a hepatólogo • TE es suficiente para sospechar cACLD: •<10 kPa descarta cACLD •Entre 10-‐15 kPa sugiere cACLD+ confirmación •>15 kPa diagnóstico de cACLD • TE útil para identificar CSPH y descartar varices Impacto elastografía-cACLD CLINICAL STAGE HISTOLOGY CLD F3 CLINICAL STAGE ELASTOGRAPHY 10+ 15 (kPa) COMPENSATED CIRRHOSIS F4 cACLD DECOMPENSATED CIRRHOSIS F4 DECOMPENSATED CIRRHOSIS Impacto elastografía-Pronóstico -100 Px -16 meses -65% CH -HVPG ≥10: 51% -Varices: 72% de CH -No tratamiento -41% alguna complicación Robic, et al. J Hepatol 2011 Impacto elastografía-Seguimiento Delta LSM Baseline LSM <21 kPa ≥21 kPa <10% ≥10% 2/57 (3.5%) 95% CI: 0-8.3% 12/37 (32.4%) 95%CI: 17.3-47.5% 4/58 (6.9%) 95% CI: 0.4-13.4% 10/33 (30.3%) 95% CI: 14.6-46% 94 pacientes con cACLD (seguimiento: 43 meses) Datos internos, Servicio Hepatología-HUVH, feb. 2016 Impacto elastografía-Seguimiento Baseline LSM <21 kPa ≥21 kPa 2/57 (3.5%) 95% CI: 0-8.3% 12/37 (32.4%) 95% CI: 17.3-47.5% Delta LSM Delta LSM <10% ≥10% <10% ≥10% 0/38 (0%) 95% CI: 0-0% 2/16 (12.5%) 95% CI: 0-28.7% 4/20 (20%) 95% CI: 2.5-37.5% 8/17 (47.1%) 95% CI: 23.3-70.8% Datos internos, Servicio Hepatología-HUVH, feb. 2016 Impacto elastografía-Seguimiento tratamiento Elastografía hepática: • Basal: 20,8 kPa (11,1-‐75) • 4 sem.: 17,5 kPa (7,8-‐48) • 12 sem.: 18,3 kPa (7,8-‐61,5) P = 0,002 P = 0,014 41 pacientes cACLD 95% genotipo1 12 sem. Simeprevir+sofosbuvir+riba Datos internos, Servicio Hepatología-HUVH, feb. 2016 Elastografía-cACLD Impacto elastografía-Seguimiento tratamiento • Elasticidad esplénica: congestión: presión portal Impacto elastografía-Seguimiento Elastografía esplénica: • Basal: 45,7 kPa (17,3-‐75) • 4 sem.: 34,8 kPa (13,9-‐75) • 12 sem.: 32,1 kPa (12,3-‐75) P = 0,175 P = 0,037 Datos internos, Servicio Hepatología-HUVH, feb. 2016 Elastografía-cACLD Impacto elastografía-Epidemiología TRANSIENT ELASTOGRAPHY LIVER BIOPSY CLINICAL DIAGNOSIS F0/1 F2 F3 ACLD-LC cACLD-varices Panelistas Baveno VI-2015 Q 2 Do you perform screening EGD in patients with ACCLD at the time of diagnosis to detect the presence of gastro esophageal varices ? 48 answers 100 Q3 If your answer was YES do you use non-invasive methods to restrict the performance of EGD to the patients at higher risk of having varices ? 48 answers 100 96 80 80 60 60 % % 40 40 20 20 0 4 Yes No 0 89 11 Yes No cACLD-varices ¿ENDOSCOPIA A TODOS LOS PACIENTES cACLD? NO cACLD-varices Augustin S, et al. J Hepatol 2013 cACLD-varices ¿Qué pacientes con cACLD pueden evitar la endoscopia de cribado? -‐TE es mejor para descartar (rule out) varices ( Se/NPV) -‐Rendimiento mejora combinando parametros clínicos: LSPS, VRS, ANTICIPATE -‐Reglas de clasificación simples y visuales funcionan mejor -‐Riesgo aceptable de varices no sospechadas: <5% VNT Baveno VI SESSION 1 – Screening and surveillance ;; invasive and non invasive methods CONSENSUS STATEMENTS IDENTIFICATION OF PATIENTS WITH cACLD WHO CAN SAFELY AVOID SCREENING ENDOSCOPY • Patients with a liver stiffness < 20 kPa and with a platelet count > 150,000 have a very low risk of having varices requiring treatment, and can avoid screening endoscopy (1b;A) • These patients can be followed up by yearly repetition of TE and platelet count (5;D) • If liver stiffness increases or platelet count declines, these patients should undergo screening EGD (5;D) cACLD-varices Descartar varices en cACLD No. All VNT Classification rule varices Augustin, et al Montes, et al 49 85 10% 45%* 0 20% All varices VNT Varices VNT Endoscopies NPV NPV missed missed avoided LSM<25 93% 100% 7% 0 61% LSM<25+Pla≥150 100% 100% 0 0 20% LSM<20 90% -‐ 9.5% -‐ 25% LSM<20 and/or Pla>120 100% 100% 0 0 15% Ding, et al 271 -‐ 10% LSM<25+Pla≥100 -‐ 100% -‐ 0 39% ANTICIPATE 379 42% 15% LSM<25+Pla≥100 79% 95% 21% 5% 45% LSM<25+Pla≥150 86% 96.5% 14% 3.5% 23% cACLD-varices ANTICIPATE STUDY Assessing noninvasive tools to identify cirrhotic portal hypertension and true risk of esophageal varices -Juan Abraldes, Michael Ney;; Edmonton, Canada -Annalisa Berzigotti, Jaime Bosch;; Barcelona, Spain -Cristophe Bureau;; Toulouse, France -Horia Stefanescu, Bodgan Procopet;; Cluj-Napoca, Romania -Salvador Augustin, Joan Genescà;; Barcelona, Spain No publicado cACLD-varices ANTICIPATE STUDY 393 patients with compensated cirrhosis 379 patients with endoscopy LSM ≥25 kPa LSM <25 kPa N =215 (57%) EV = 56 (26%) VNT = 19 (9%) N =164 (43%) EV = 104 (63%) VNT = 37 (23%) Plat ≥ 150 000 Plat < 150 000 Plat ≥ 150 000 Plat < 150 000 N = 86 (23%) EV = 12 (14%) VNT = 3 (3.5%) N = 129 (34%) EV = 44 (34%) VNT = 16 (12%) N = 46 (12%) EV = 22 (48%) VNT = 8 (17%) N = 118 (31%) EV = 82 (69%) VNT = 29 (25%) cACLD-CSPH ¿Qué pacientes se pueden clasificar como pacientes con CSPH? -‐TE mejor para asegurar (rule in) CSPH ( Es/PPV) -‐Rendimiento mejora poco combinando paramétros cínicos: LSPS, PHRS, ANTICIPATE -‐Reglas de clasificación simples y visuales funcionan mejor -‐PPV de CSPH: 90% Baveno VI SESSION 1 – Screening and surveillance ;; invasive and non invasive methods CONSENSUS STATEMENTS DIAGNOSIS OF CSPH IN PATIENTS WITH cACLD • HVPG measurement is the gold-‐standard method to assess the presence of clinically significant portal hypertension, which is defined as HVPG≥10 mmHg (1b;A) • By definition, patients without CSPH have no gastroesophageal varices, and have a low 5-‐yr risk of developing them (1b;A) • In patients with virus related cACLD non-‐invasive methods are sufficient to rule-‐in CSPH, defining the group of patients at risk of having endoscopic signs of PH. The following can be used (2b; B): Baveno VI SESSION 1 – Screening and surveillance ;; invasive and non invasive methods CONSENSUS STATEMENTS DIAGNOSIS OF CSPH IN PATIENTS WITH cACLD (II) • Liver stiffness by TE (≥20-‐25 kPa; at least two measurements on different days in fasting condition; caution should be paid to flares of ALT; refer to EASL guidelines for correct interpretation criteria), alone or combined to Plt and spleen size • The diagnostic value of TE for CSPH in other etiologies remains to be ascertained (5;D) • Imaging showing collateral circulation is sufficient to rule-‐in CSPH in patients with cACLD of all etiologies (2b;B) cACLD-CSPH ANTICIPATE STUDY 393 patients with compensated cirrhosis 182 HVPG CSPH 109 (60%) LSM ≥25 kPa LSM <25 kPa N =115 (63%) CSPH = 45 (39%) N =67 (37%) CSPH = 64 (96%) Plat ≥ 150 000 Plat < 150 000 Plat ≥ 150 000 Plat < 150 000 N = 46 (25%) CSPH = 8 (17%) N = 69 (38%) CSPH = 37 (54%) N = 17 (9%) CSPH = 16 (94%) N = 50 (28%) CSPH = 48 (96%) cACLD-CSPH ANTICIPATE STUDY 393 patients with compensated cirrhosis 182 HVPG CSPH 109 (60%) LSM ≥25 kPa LSM <25 kPa N =115 (63%) CSPH = 45 (39%) Plat ≥ 150 000 Plat < 150 000 N = 46 (25%) CSPH = 8 (17%) N = 69 (38%) CSPH = 37 (54%) N =67 (37%) CSPH = 64 (96%) cACLD-CSPH 5 10 HVPG (mmHg) 20kPa: 85-‐90% ELASTOGRAPHY (PPV) 25kPa: 95% 30kPa: 100% Resumen RESUMEN -‐Los tests no invasivos (TE) tienen un gran impacto en el manejo de la EHC -‐El nuevo concepto de cACLD será útil para la práctica clínica y la investigación -‐El cribado de varices puede evitarse en un grupo substancial de pacientes con cACLD mediante reglas de clasificación simples utilizando TE y recuento de plaquetas -‐Mediante la elastografía se puden seleccionar pacientes con CSPH -‐Otros pruebas no invasivas similares a la TE probablemente sean igualmente útiles CLINICAL STAGE CLD HISTOLOGY F3 HVPG 5 (mmHg) CLINICAL STAGE ELASTOGRAPHY 10+ 15 (kPa) VARICES EARLY COMPENSATED CIRRHOSIS F4 LATE DECOMPENSATED COMPENSATED CIRRHOSIS CIRRHOSIS F4 F4 10 EARLY cACLD LATE cACLD 20-‐30 (25) DECOMPENSATED CIRRHOSIS GRACIAS Baveno VI SESSION 1 – Screening and surveillance ;; invasive and non invasive methods CONSENSUS STATEMENTS DEFINITION OF COMPENSATED ADVANCED CHRONIC LIVER DISEASE (cACLD) • The introduction of transient elastography in clinical practice has allowed the early identification of patients with chronic liver disease (CLD) at risk of developing clinically significant portal hypertension (CSPH) (1b;A). • For these patients, the alternative term “compensated advanced chronic liver disease (cACLD)” has been proposed to better reflect that the spectrum of severe fibrosis and cirrhosis is a continuum in asymptomatic patients, and that distinguishing between the two is often not possible on clinical grounds. (5; D) Baveno VI SESSION 1 – Screening and surveillance ;; invasive and non invasive methods CONSENSUS STATEMENTS DEFINITION OF COMPENSATED ADVANCED CHRONIC LIVER DISEASE (cACLD) (II) • Currently, both terms : “cACLD” and “compensated cirrhosis” are acceptable. (5; D) • Patients with suspicion of cACLD should be referred to a liver disease specialist for confirmation, follow-‐ up and treatment (5;D) Baveno VI SESSION 1 – Screening and surveillance ;; invasive and non invasive methods CONSENSUS STATEMENTS CRITERIA TO SUSPECT cACLD • Liver stiffness by transient elastography is sufficient to suspect cACLD in asymptomatic subjects with known causes of CLD (1b;A) • Transient elastography often has false positive results; hence 2 measurements on different days are recommended in fasting conditions (5;D) • TE values < 10 kPa in the absence of other known clinical signs rule-‐out cACLD; values between 10 and 15 kPa are suggestive of cACLD but need further test for confirmation; values > 15 kPa are highly suggestive of cACLD (1b;A) Baveno VI SESSION 1 – Screening and surveillance ;; invasive and non invasive methods CONSENSUS STATEMENTS CRITERIA TO CONFIRM cACLD • Invasive methods are employed in referral centers in a stepwise approach when the diagnosis is in doubt or as confirmatory tests • Methods and findings that confirm the diagnosis of cACLD are : – Liver biopsy showing severe fibrosis or established cirrhosis (1a;A); collagen proportionate area (CPA) measurement on histology provides quantitative data on the amount of fibrosis and holds prognostic value (2b;B) and its assessment is recommended (5;D) – Upper GI endoscopy showing gastroesophageal varices (1b;A) – Hepatic venous pressure gradient (HVPG) measurement; values > 5 mmHg indicate sinusoidal portal hypertension (1b;A) cACLD-varices Criterios de validación/utilización de reglas clasificación exclusión de varices -‐Pacientes con cACLD detectados por elastografía -‐Diseño secuencial y prospectivo -‐Evaluación por etiologías -‐Exclusión pacientes con riesgo elevado de varices: -‐Descompensados -‐Child B-‐C -‐Circulación colateral evidente en imagen -‐Varices conocidas Impacto elastografía-Pronóstico All patients HCV Llop, et al. J Hepatol 2012 cACLD-varices ANTICIPATE STUDY 393 patients with compensated cirrhosis 379 patients with endoscopy LSM ≥25 kPa LSM <25 kPa N =215 (57%) EV = 56 (26%) VNT = 19 (9%) N =164 (43%) EV = 104 (63%) VNT = 37 (23%) Plat ≥ 100 000 Plat < 100 000 Plat ≥ 100 000 Plat < 100 000 N = 170 (45%) EV = 36 (21%) VNT = 8 (5%) N = 45 (12%) EV = 20 (44%) VNT = 11 (24%) N = 92 (24%) EV = 48 (52%) VNT = 16 (17%) N = 72 (19%) EV = 56 (78%) VNT = 21 (29%) cACLD-CSPH ANTICIPATE STUDY 393 patients with compensated cirrhosis 182 HVPG CSPH 109 (60%) LSM ≥25 kPa LSM <25 kPa N =115 (63%) CSPH = 45 (39%) Plat ≥ 150 000 Plat < 150 000 N = 46 (25%) CSPH = 8 (17%) N = 69 (38%) CSPH = 37 (54%) N =67 (37%) CSPH = 64 (96%)
